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Bonjour J.-P.,University of Geneva | Benoit V.,Yoplait | Atkin S.,Diabetes and endocrinology research Center
Journal of Nutrition, Health and Aging | Year: 2015

Objective: To evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum parathyroid hormone (PTH) and bone resorption markers (BRM) as compared to iso-caloric and iso-protein dairy products in aged white women at risk of fragility fractures.Design: A randomized double-blind controlled trial.Setting: A community dwelling home.Participants: Forty-eight women over 60 years (mean age 73.4).Intervention: Consumption during 84 days of two 125 g servings of either vitamin D and calcium-fortified yogurts (FY) at supplemental levels of 10 µg vitamin D3/d and 520 mg/d of calcium (total=800 mg/d), or non fortified control yogurts (CY) providing 280 mg/d of calcium.Measurements: Serum changes from baseline (D0) to D28, D56 and D84 in 25OHD, PTH and in two BRM: Tartrate-resistant-acid-phosphatase-isoform-5b (TRAP5b) and carboxy-terminal-cross-linked-telopeptide of type-I-collagen (CTX).Results: The 10 years risk of major and hip fractures were 13.1 and 5.0%, and 12.9 and 4.2 %, in FY and CY groups, respectively. From D0 to D84, serum 25OHD increased (mean±SE) from 34.3±2.4 to 56.3±2.4 nmol/L in FY (n=24) and from 35.0±2.5 to 41.3±3.0 nmol/L in CY (n=24), (P=0.00001). The corresponding changes in PTH were from 64.1±5.1 to 47.4±3.8 ng/L in FY and from 63.5±4.6 to 60.7±4.2 ng/L in CY (P=0.0011). After D84, TRAP5b was reduced significantly (P=0.0228) and CTX fell though not significantly (P=0.0773) in FY compared to CY.Conclusion: This trial in aged white women living in a community dwelling home at risk for osteoporotic fractures confirms that fortification of dairy products with vitamin D3 and calcium should provide a greater prevention of secondary hyperparathyroidism and accelerated bone resorption as compared to non-fortified equivalent foods. © 2015, Serdi and Springer-Verlag France. Source


Sekhar R.V.,Diabetes and endocrinology research Center | Jahoor F.,Baylor College of Medicine | Iyer D.,Diabetes and endocrinology research Center | Guthikonda A.,Diabetes and endocrinology research Center | And 4 more authors.
Metabolism: Clinical and Experimental | Year: 2012

Patients with HIV-associated dyslipidemic lipodystrophy (HADL) have characteristic lipid kinetic defects: accelerated lipolysis, blunted fat oxidation and increased hepatic fatty acid reesterification. HADL patients with lipoatrophy also have leptin deficiency. Small or non-randomized studies have suggested that leptin replacement improves glucose metabolism in HADL, with very limited data regarding its effects on the lipid kinetic abnormalities. We performed a randomized, double-blind, placebo-controlled, dose-escalating (0.02 mg/kg/d for two months; 0.04 mg/kg/d for a further two months) study of the effects of metreleptin on lipid kinetics in 17 adults with HADL, hypertriglyceridemia and hypoleptinemia. Rates of lipolysis, intra-adipocyte and intrahepatic reesterification and fatty acid oxidation were measured using infusions of 13C1-palmitate and 2H 5-glycerol, and indirect calorimetry. Fasting lipid profiles and glucose and insulin responses to oral glucose challenge were also measured. Metreleptin treatment induced significant, dose-dependent increases in fasting plasma leptin levels. There was no significant change in total lipolysis, net lipolysis, adipocyte or hepatic re-esterification or fatty acid oxidation, or in fasting triglyceride or HDL-C concentrations, with metreleptin treatment. Metreleptin decreased fasting non-HDL-C levels (P <.01) and area-under-the-curve for glucose (P <.05). In hypoleptinemic HADL patients, treatment with metreleptin at 0.02 or 0.04 mg/kg/d does not improve abnormal fasting lipid kinetics, or triglyceride or HDL-C levels. Metreleptin does, however, improve glycemia and non-HDL-C in these patients. These results suggest a dissociation between leptin's effects on glucose metabolism compared to those on lipid kinetics in HADL. © 2012 Elsevier Inc. Source


Zhou J.,Chongqing Medical University | Zhou J.,Diabetes and endocrinology research Center | Chan L.,Diabetes and endocrinology research Center | Zhou S.,Chongqing Medical University
Current Medicinal Chemistry | Year: 2012

There is evidence that Trigonella foenum-graecum L. (fenugreek), a traditional Chinese herb, and its components are beneficial in the prevention and treatment of diabetes and central nervous system disease. The pharmacological activities of trigonelline, a major alkaloid component of fenugreek, have been more thoroughly evaluated than fenugreek's other components, especially with regard to diabetes and central nervous system disease. Trigonelline has hypoglycemic, hypolipidemic, neuroprotective, antimigraine, sedative, memory-improving, antibacterial, antiviral, and anti-tumor activities, and it has been shown to reduce diabetic auditory neuropathy and platelet aggregation. It acts by affecting .. cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability. However, further study of trigonelline's pharmacological activities and exact mechanism is warranted, along with application of this knowledge to its clinical usage. This review aims to give readers a survey of the pharmacological effects of trigonelline, especially in diabetes, diabetic complications and central nervous system disease. In addition, because of its pharmacological value and low toxicity, the reported adverse effects of trigonelline in experimental animal models and humans are briefly reviewed, and the pharmacokinetics of trigonelline are also discussed. © 2012 Bentham Science Publishers. Source


Chen W.,Diabetes and endocrinology research Center | Chang B.,Diabetes and endocrinology research Center | Saha P.,Diabetes and endocrinology research Center | Li L.,Diabetes and endocrinology research Center | And 5 more authors.
Molecular and Cellular Biology | Year: 2012

Mutations in BSCL2 underlie human congenital generalized lipodystrophy. We inactivated Bscl2 in mice to examine the mechanisms whereby absence of Bscl2 leads to adipose tissue loss and metabolic disorders. Bscl2 -/- mice develop severe lipodystrophy of white adipose tissue (WAT), dyslipidemia, insulin resistance, and hepatic steatosis. In vitro differentiation of both Bscl2 -/- murine embryonic fibroblasts (MEFs) and stromal vascular cells (SVCs) reveals normal early-phase adipocyte differentiation but a striking failure in terminal differentiation due to unbridled cyclic AMP (cAMP)-dependent protein kinase A (PKA)-activated lipolysis, which leads to loss of lipid droplets and silencing of the expression of adipose tissue-specific transcription factors. Importantly, such defects in differentiation can be largely rescued by inhibitors of lipolysis but not by a gamma peroxisome proliferator-activated receptor (PPARγ) agonist. The residual epididymal WAT (EWAT) in Bscl2 -/- mice displays enhanced lipolysis. It also assumes a "brown-like" phenotype with marked upregulation of UCP1 and other brown adipose tissue-specific markers. Together with decreased Pref1 but increased C/EBPβ levels, these changes highlight a possible increase in cAMP signaling that impairs terminal adipocyte differentiation in the EWAT of Bscl2 -/- mice. Our study underscores the fundamental role of regulated cAMP/PKA-mediated lipolysis in adipose differentiation and identifies Bscl2 as a novel cell-autonomous determinant of activated lipolysis essential for terminal adipocyte differentiation. © 2012, American Society for Microbiology. Source


Nguyen D.,Baylor College of Medicine | Nguyen D.,Diabetes and endocrinology research Center | Hsu J.W.,U.S. Department of Agriculture | Jahoor F.,U.S. Department of Agriculture | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Background: HIV-infected patients are reported to have impaired oxidation of fatty acids despite increased availability, suggesting a mitochondrial defect. We investigated whether diminished levels of a key mitochondrial antioxidant, glutathione (GSH), was contributing to defective fatty acid oxidation in older HIV-infected patients, and if so, the metabolic mechanisms contributing to GSH deficiency in these patients. Methods: In an open-label design, 8 older GSH-deficient HIV-infected males were studied before and after 14 days of oral supplementation with the GSH precursors cysteine and glycine. A combination of stable-isotope tracers, calorimetry, hyperinsulinemic-euglycemic clamp, and dynamometry were used to measure GSH synthesis, fasted and insulin-stimulated (fed) mitochondrial fuel oxidation, insulin sensitivity, body composition, anthropometry, forearm-muscle strength, and lipid profiles. Results: Impaired synthesis contributed to GSH deficiency in the patients and was restored with cysteine plus glycine supplementation. GSH improvement was accompanied by marked improvements in fasted and fed mitochondrial fuel oxidation. Associated benefits included improvements in insulin sensitivity, body composition, anthropometry, muscle strength, and dyslipidemia. Conclusions: This work identifies 2 novel findings in older HIV-infected patients: 1) diminished synthesis due to decreased availability of cysteine and glycine contributes to GSH deficiency and can be rapidly corrected by dietary supplementation of these precursors and 2) correction of GSH deficiency is associated with improvement of mitochondrial fat and carbohydrate oxidation in both fasted and fed states and with improvements in insulin sensitivity, body composition, and muscle strength. The role of GSH on ameliorating metabolic complications in older HIV-infected patients warrants further investigation. (J Clin Endocrinol Metab 99: 169-177, 2014). © Copyright 2014 by The Endocrine Society. Source

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